The Finding

Andrew Fire, a biologist at Stanford University, along with his graduate student Ivan Nikolay Zheludev and other colleagues, delved into an RNA database containing thousands of sequences of single-stranded circular RNA from human stool samples.

RNA, or ribonucleic acid, resembles DNA, but instead of a double-stranded helix of base pairs, it consists of a single strand. RNA typically translates instructions from DNA to create functional products like proteins.

Over 200 viruses, such as Covid-19, Ebola, and various flu strains, contain RNA genomes that enable them to bypass DNA. These viral genomes consist of RNA sequences that form a protective shell and ribozymes—enzymes that assist in viral replication inside host cells.

However, the Stanford team identified thousands of unique RNA loops that did not follow the typical DNA coding path for proteins. This behavior is reminiscent of viroids, which are even tinier than viruses.

While the researchers acknowledged the similarities, they classified these findings as a new type of biological entity that exists between the two.

In their study, they referred to these structures as “viroid-like colonists of the human microbiome” but named them “obelisks” due to their rod-like shape formed by two genes self-organizing. This nomenclature allows flexibility in case they turn out to be similar to RNA plasmids, another form of genetic material found in bacteria.

After identifying the obelisks, the team analyzed microbiome data from the mouths and guts of 472 individuals from prior studies, discovering obelisks in nearly 10 percent of samples.

Though the study is in preprint form, uploaded to the BioRxiv server on January 21, 2024, and not yet peer-reviewed, it has already generated considerable interest, with major scientific publications like Science and Nature extensively covering the findings.

Microbiologist Kathleen Hefferon from Cornell University, who did not partake in the research, described the results as “super thrilling,” while Saima May Sidik, a microbiologist-turned-journalist, termed it “wildly weird” in her Nature article.

What Are the Obelisks?

So, what exactly are these peculiar obelisks found within us? Researchers are still piecing together the puzzle, but to grasp what they have uncovered, we must dive into the microscopic realm.

Ed Feil, a Professor of Microbial Evolution at the Milner Centre for Evolution at the University of Bath, England, stated in The Conversation:

> “Things can get weirder and the rules fuzzier as we move through smaller and smaller scales.”

Let’s begin with viruses, which are on the larger end of the scale, then transition to viroids, and finally, to the newly discovered obelisks.

Viruses

Scientists have a comprehensive understanding of viruses. It's estimated there are around ten nonillion unique viruses on Earth.

To put this into context, one million seconds equals about 11.6 days, a billion seconds is approximately 31.7 years, a trillion seconds amounts to about 31.7 thousand years, and a quadrillion seconds is nearly 31.7 million years—leading to the conclusion that 10 nonillions of seconds would break any calculator.

Viruses inhabit every known environment and have likely shaped the evolutionary paths of life by infecting and manipulating their hosts. As they require a host for replication, they exist at the very edge of what we define as life.

Viroids

In contrast, viroids are even smaller than viruses. Composed solely of RNA fragments, they cannot synthesize proteins, making them even closer to the brink of life than viruses. Unlike viruses, viroids lack a protective shell to safeguard their genomes.

Similar to viruses, viroids need a host to replicate and can induce disease and infections. They have primarily been identified in flowering plants, fungi, and a few animals.

Obelisks

The unique obelisks discovered by the Stanford team share traits with viroids, which is why the preprint refers to them as "viroid-like," but they also exhibit characteristics of viruses.

Feil noted in The Conversation that these obelisks consist of circular, single-stranded RNA genomes without a protective protein shell, akin to viroids. However, they also appear to contain genes that are predicted to code for proteins, similar to viruses.

What sets the obelisks apart is their shape and structure. Unlike the flat, circular RNA of viroids, these obelisks are rolled into a rod shape, and their RNA sequences differ from those found in viroids. Additionally, while viroids and viruses typically rely on more complex organisms for hosts, the obelisks seem to prefer bacterial cells.

How Common Are They?

With the confirmation of obelisks, the next question arises: how prevalent are they? The Stanford researchers found not just a single type, but nearly 30,000 unique obelisk variants in the microbiomes of people from diverse backgrounds globally.

Specifically, their analysis of human microbial databases revealed the presence of obelisks in half of the bacteria found in human mouths and 7 percent of gut bacteria. However, further research is required to validate these findings.

While obelisks seem widespread, the types identified vary depending on the body location and individual. Longitudinal data indicates that at least one type of obelisk can persist in a person for about a year.

Scientists have established that obelisks dwell within bacteria rather than more complex hosts like viruses, suggesting that they replicate within their microbial hosts. However, the specific bacterial species that favor hosting the obelisks remain uncertain.

Helpful or Harmful?

The discovery of obelisks within us is groundbreaking, but the next step for scientists is to determine their role—whether they are beneficial or harmful.

Despite their small size compared to viruses, obelisks still transmit instructions to cells, though their messages remain unclear.

What researchers do know is that all identified obelisks encode a specific protein they have dubbed “oblin,” with many also encoding a smaller variant. Feil mentions in The Conversation:

> “Obulins bear no evolutionary resemblance, or ‘homology,’ to any other protein found, and there are few clues as to their function.”

Consequently, scientists are eager to explore these newly discovered obelisks and the oblins they produce to ascertain their implications for human health.

Looking to the Future

Fortunately, the researchers identified a bacterial host, Streptococcus sanguinis, in dental plaque, that consistently harbors at least one type of obelisk. This bacterial strain is also straightforward to cultivate and study in a lab, providing a valuable model for biologists to investigate the fundamentals of obelisks.

Some experts speculate that studying obelisks might aid in tracing the origins of life, as scientists believe viroids and their relatives could be some of the oldest, most primitive life forms still in existence.

Thus, a central question for researchers is the evolutionary timeline: Did viruses evolve before viroids and obelisks, or did viroids and obelisks come first?

Naturally, scientists are also curious about the obelisks' ability to infect various life forms and whether they have played a role in shaping the multitude of species present today, for better or worse.

Feil suggests that it’s equally plausible for bacterial hosts to have evolved mechanisms to recruit obelisks for some unspecified advantage as it is for them to have developed defenses against them. The same consideration applies to our human microbiome. At this moment, the obelisks residing within our microbiome could possess therapeutic potential or harmful effects.

Perspective Shift

This highlights a significant point: It’s 2024, and scientists continue to uncover new aspects of our biology. How many more secrets lie within us? Although we believe we understand a lot, particularly what is pertinent, the reality is that we remain unaware of the vast unknown—obelisks serve as a recent reminder.

On one hand, this truth is exhilarating, promising future discoveries that could challenge our current understanding. On the other hand, it serves as a cautionary note that as we experiment with our bodies for scientific advancement, we may inadvertently interfere with crucial yet unidentified elements.

It raises the question of whether we will one day find it difficult to discern which aspects of our bodies function naturally and which have been altered by human intervention.

This article originally appeared in the author’s newsletter, Curious Adventure. It has been edited and republished on Medium with her permission.

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